chr16-89285522-C-T

Position:

chr16-89285522-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_013275.6(ANKRD11):c.1020G>A(p.Thr340Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,614,004 control chromosomes in the GnomAD database, including 303 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 23 hom., cov: 32)

Exomes 𝑓: 0.019 ( 280 hom. )

Consequence

ANKRD11
NM_013275.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

ANKRD11 (HGNC:21316): (ankyrin repeat domain containing 11) This locus encodes an ankryin repeat domain-containing protein. The encoded protein inhibits ligand-dependent activation of transcription. Mutations in this gene have been associated with KBG syndrome, which is characterized by macrodontia, distinctive craniofacial features, short stature, skeletal anomalies, global developmental delay, seizures and intellectual disability. Alternatively spliced transcript variants have been described. Related pseudogenes exist on chromosomes 2 and X. [provided by RefSeq, Jan 2012]

ANKRD11 links:

ANKRD11 (HGNC:):

ANKRD11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003126055).

BP6

Variant 16-89285522-C-T is Benign according to our data. Variant chr16-89285522-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 585398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-89285522-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.05 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0146 (2217/152296) while in subpopulation NFE AF= 0.02 (1362/68030). AF 95% confidence interval is 0.0191. There are 23 homozygotes in gnomad4. There are 1073 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2217 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD11	NM_013275.6 linkuse as main transcript	c.1020G>A	p.Thr340Thr	synonymous_variant	9/13	ENST00000301030.10	NP_037407.4	Q6UB99
ANKRD11	NM_001256182.2 linkuse as main transcript	c.1020G>A	p.Thr340Thr	synonymous_variant	10/14		NP_001243111.1	Q6UB99
ANKRD11	NM_001256183.2 linkuse as main transcript	c.1020G>A	p.Thr340Thr	synonymous_variant	9/13		NP_001243112.1	Q6UB99

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD11	ENST00000301030.10 linkuse as main transcript	c.1020G>A	p.Thr340Thr	synonymous_variant	9/13	5	NM_013275.6	ENSP00000301030.4		Q6UB99

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2218

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00449

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0201

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00871

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0200

Gnomad OTH

AF:

0.0287

GnomAD3 exomes

AF:

0.0166

AC:

4163

AN:

251444

Hom.:

AF XY:

0.0174

AC XY:

2362

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00412

Gnomad AMR exome

AF:

0.0169

Gnomad ASJ exome

AF:

0.0243

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0111

Gnomad FIN exome

AF:

0.0164

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.0222

GnomAD4 exome

AF:

0.0187

AC:

27339

AN:

1461708

Hom.:

280

Cov.:

AF XY:

0.0186

AC XY:

13552

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.00356

Gnomad4 AMR exome

AF:

0.0172

Gnomad4 ASJ exome

AF:

0.0235

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.0171

Gnomad4 NFE exome

AF:

0.0204

Gnomad4 OTH exome

AF:

0.0171

GnomAD4 genome

AF:

0.0146

AC:

2217

AN:

152296

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1073

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00448

Gnomad4 AMR

AF:

0.0200

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00892

Gnomad4 FIN

AF:

0.0155

Gnomad4 NFE

AF:

0.0200

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0185

Hom.:

Bravo

AF:

0.0150

TwinsUK

AF:

0.0240

AC:

ALSPAC

AF:

0.0234

AC:

ESP6500AA

AF:

0.00660

AC:

ESP6500EA

AF:

0.0230

AC:

198

ExAC

AF:

0.0161

AC:

1956

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0232

EpiControl

AF:

0.0256

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 01, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

KBG syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 13, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.2

DANN

Benign

0.63

DEOGEN2

Benign

0.011

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0031

Sift4G

Benign

0.65

Vest4

0.21

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over